Three mechanisms of immune-mediated cytotoxicity will be evaluated in terms of their possible roles in the pathogenesis of naturally occurring polymyositis and experimental autoimmune myositis in the dog using an in vitro myotoxicity assay system. This approach has the distinct advantage of the comprehensive comparison of both a naturally occurring disease and an experimental disease model in the same specie. The assay system is based or creatine phosphokinase activity released from tissue cultures derived from both normal and polymyositis canine muscle explants challenged with humoral, cellular, and humoral-dependent cell-mediated mechanisms of cytotoxicity. In addition to the investigation of the pathogenesis of polymyositis, the effects of specific immune mechanisms on the passive and active electrical properties of excitable membranes will be investigated. Using special computerized intracellular microelectrode techniques, changes in specific transmembrane ionic conductances and excitability properties of the sarcolemma produced by humoral and cell-mediated immune mechanisms will be determined in both natural and experimental disease and in vitro models of disease. This objective of this combined immunological and electrophysiological approach to the problem of immune-mediated disease of muscle are directed toward a more rational approach to the diagnosis and treatment of immune-mediated diseases of excitable tissues based on a keener understanding of the pathogenesis and pathophysiology of such diseases.